rs267606892

Positions:

• chrM-10563-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The ENST00000361335.1(MT-ND4L):​c.94T>C​(p.Cys32Arg) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-ND4L ENST00000361335.1 missense
• Scores: Apogee2 Pathogenic 0.84
• Clinical Significance: Pathogenic no assertion criteria provided P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.73

Genes affected

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Apogee2 supports a deletorius effect, 0.84026223 >= 0.5 .
• PP5: Variant M-10563-T-C is Pathogenic according to our data. Variant chrM-10563-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 9706.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND4L	ENST00000361335.1	c.94T>C	p.Cys32Arg	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap

No disease associated.

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial colorectal cancer Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.84
Hmtvar	Pathogenic	0.89
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.13	T
DEOGEN2	Benign	0.20	T
LIST_S2	Benign	0.81	T
MutationTaster	Benign	1.0	A
PROVEAN	Pathogenic	-12	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
GERP RS		5.1
Varity_R		0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs267606892; hg19: chrM-10564;